Insufficient sleep in later life is thought to contribute to declines in physical and mental functioning, and increase risk for morbidity and mortality. A yet unanswered question is: how does poor sleep contributes to worse health, particularly in aging. Both inflammation and cellular stress, which contribute to aging of cells, are proposed biological pathways through which sleep loss influences disease. I propose that sleep deprivation in older adults will alter the intracellular environment, decrease telomerase, and increase gene expression patterns consistent with cellular stress responses, inflammatory activity, and senescent signal expression. The over-arching objective of this proposal is to apply a biobehavioral framework to study the sleep-health relationship in older adults. Aims. To do this I will: 1) obtain training in sleep, aging, and gene expression, 2) test biobehavioral mechanisms of sleep loss on health by conducting analyses using the Multi-Ethnic Study of Atherosclerosis (MESA), examining the contribution of sleep disturbances, sleep quantity, and sleep depth to rates of telomere attrition over 10 years, and 3) experimentally test the inflammatory, cellular stress, and cell senescence gene expression pathways that are disrupted from one night (Study 2) and 12 weeks (Study 3) of partial sleep deprivation in older adults (ages 60+). Significance. This unique interdisciplinary work will advance the field of biomedical sleep research by better defining one of the biological mechanisms through which sleep influences disease vulnerability in late life.